Summary of the Profiles

Summary of the Biomarkers

Histamine is a compound that affects immune response, physiological function of the digestive tract, and acts as a neurotransmitter.

Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions.

Advanced Intestinal Barrier Assessment 5150:

DAO

Histamine

Zonulin

Why Test Diamine Oxidase (DAO)?

Diamine oxidase is the body’s primary enzyme for breaking down ingested histamine and a natural defense against histamine excess. If you ingest too much dietary histamine or produce more than your DAO level can handle, reactions can occur. DAO is produced in the small intestine but certain drugs, foods and bacteria may suppress its production.

Low DAO levels are associated with the following symptoms and conditions:

Migraine, headache

Chronic fatigue

Hives, skin rash, eczema, psoriasis

Nasal congestion, asthma

Gastrointestinal disorders, inflammation, irritable bowel syndrome

Dysmenorrhea, PMS, estrogen dominance

Arrhythmia, hypertension, hypotension

Fibromyalgia, muscular pain

Rheumatoid arthritis

Neurological conditions such as multiple sclerosis and attention deficit and hyperactivity disorder (in childhood and adolescence)

Depression and anxiety

Symptoms of low DAO are similar to those of histamine excess since it is the DAO that breaks down and metabolizes the histamine. Patients suffering from urticaria (hives), Crohn’s or celiac disease show low DAO activity in serum or plasma.1,2 People with the inability to break down histamine react to many substances and will often improve on antihistamines. Since DAO is made in the gastrointestinal tract, low levels are also indicative of poor digestive function and a compromised intestinal barrier.

Why Test Histamine?

Histamine is involved in many types of allergic and inflammatory processes, including immediate and delayed hypersensitivity reactions. It also acts as a neurotransmitter and regulates physiological function in the gastrointestinal tract. Histamine imbalances in the body may cause a variety of adverse effects ranging from life-threatening allergic reactions to localized itching, runny nose or hives.

An excess of histamine may be a result of ingested histamine (certain foods), released histamine from storage sites in the body (from food or environmental triggers), or a diamine oxidase deficiency (needed for the breakdown of histamine). Testing histamine along with diamine oxidase (DAO) levels provides important information that standard food sensitivity tests may not reveal. In fact, many clinicians often suspect food sensitivities when the culprit may actually be histamine intolerance. An excellent full text review of histamine intolerance is available. 3

High histamine levels are associated with the following symptoms and conditions:

Severe allergic reactions (anaphylaxis)

Low muscle tone

High blood pressure

Dizziness

Headache

Nausea, vomiting

Diarrhea, gas

Intestinal cramps

Painful menstruation

Shortness of breath

Congestion, runny nose, sneezing

Hives, itching, flushing

Abnormal heart rate

Changes in:

Circadian rhythm

Body temperature

Food intake

Learning

Memory

Locomotion

Low histamine levels are associated with the following symptoms and conditions:

Fatigue

Depression

Sleep-wake disorders such as narcolepsy

Convulsions

Seizures

What is The DAO: Histamine Ratio?

The DAO: Histamine Ratio helps detect subtle imbalances between histamine and DAO levels. Even if the DAO enzyme level is normal when histamine is high, symptoms can occur. A low ratio indicates that there may not be enough of the DAO enzyme relative to the amount of histamine in your body.

Why Test Zonulin? (5150)

Zonulin plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during conditions such sepsis might be pivotal and has been described in various experimental involving human studies. As mentioned previously, increased levels of zonulin could also be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. Therefore we measure this molecule as a non-invasive marker of gut wall integrity.

What Should I Do Before I Take This Test?

Inform your practitioner of all medications and supplements you are currently taking.

Arrange plasma collection for Monday-Thursday.

See blood draw collection instructions inside test kit.

How Are Imbalances in DAO, Histamine and Zonulin Treated?

When DAO or histamine is imbalanced, the main focus of treatment is to increase DAO, reduce histamine, and heal the gut. The primary focus of treatment for elevated zonulin levels is to correct intestinal permeability and restore a healthy balance of gut flora. Treatments might include dietary changes, enzymes, probiotics, antimicrobial herbal formulas, and supplements designed to improve the integrity of the gastrointestinal lining.

Further Testing

LPS lipopolysaccharide

LPS can be used to detect a disregulated cell membrane making it a marker of transcellular leaky gut. Since there will always be some LPS present, there should in turn be some immune response recorded. When a patient tests on the low end of the spectrum for an immune response for LPS IgG, LPS IgA and LPS IgM, this is a good indication that their immune system is not functioning as it should. When there is a low response this means immunoglobulin levels go down and bacterial levels stay up. Ongoing gut pain and flairs persist, as patients can no longer fight infections as they should and the higher level of bacteria in the gut causes irritation. Conditions associated with low LPS antibodies are IBS, Crohns Disease and Colitis.

Treatment Options:

*Berberines : to fight bacteria.

*Probiotics: to build up good flora.

*Support the immune system with immunoglobulin's, vitamin A, amino acids and proteins.

High LPS

An elevated lipopolysaccharide (LPS) reaction indicates intestinal permeability or “leaky gut.” Lipopolysaccharide is the immunogenic portion, as well as the major constituent, of the outer cell membrane of gram-negative bacteria. LPS is a bacterial endotoxin made by bacteria in the body.

When lipopolysaccharides are high in the blood, it means they are passing not only between intestinal cells, but also directly through the cells, potentially causing neuroinflammation 6 and brain injury.7 When LPS is absorbed into systemic circulation it can elicit a strong immune response.

This indicates that the immune system is actively fighting bacterial overload. Treatments include antimicrobials to lower bacterial load.

LPS High IgM : Low IgG

A high IgM with a Low IgG means there was poor seroconversion to a matured response to LPS. Antimicrobial therapies and immunoglobulins will support improvement in these areas.

Low LPS

There is clinical importance to having a low immune reaction to LPS antibodies. Since there will always be some LPS present, there should be an immune response recorded. When a patient tests on the low end of the spectrum for an immune response for LPS IgG, LPS IgA and LPS IgM, this is a good indication that their immune system is not functioning as it should. When there is a low response this means immunoglobulin levels go down and bacterial levels stay up. Ongoing gut pain and flairs persist, as patients can no longer fight infections as they should and the higher level of bacteria in the gut causes irritation.

Low LPS Antibodies are associated with an immune system that is chronically worn down. IBS and IBD can both be a result of an infection that was chronic and that has resulted in little to no immune reserve. Immunoglobulins are an excellent intervention. Adequate Vitamin A and D as well as adequate protein can also help to increase levels.